Point Prevalence of Adult Intestinal Failure in Republic Of Ireland.

Parenteral Nutrition (PN) is a life-saving treatment used for patients with Intestinal Failure (IF). PN is complex and demands highly specialised care to avoid serious complications in the home setting. All tertiary centres in the Republic of Ireland (ROI) were contacted to assess the prevalence of IF requiring PN and complications, over a one year period. Sixty-seven patients were treated across 15 centres: a period prevalence of 14.6 and 9.6 patients per million for long-term PN and home PN respectively. Three-quarters of patients experienced at least one major complication with 18% mortality rate over the study period. There were 2.86 admissions per HPN patient, each lasting mean 13.4 days. One-third experienced catheter-related infections. There was a reduced length of stay during emergency re-admissions in high volume centres (mean 31 v 43 days, p=0.17). The establishment of a National Centre for IF/HPN in ROI is integral to reducing PN-associated complications.

Multimodal analgesia using intrathecal diamorphine, and paravertebral and rectus sheath catheters are as effective as thoracic epidural for analgesia post-open two-phase esophagectomy within an enhanced recovery program.

Thoracic epidural (TE) analgesia has been the standard of care for transthoracic esophagectomy patients since the 1990s. Multimodal anesthesia using intrathecal diamorphine, local anesthetic infusion catheters (LAC) into the paravertebral space and rectus sheaths and intravenous opioid postoperatively represent an alternative option for postoperative analgesia. While TE can provide excellent pain control, it may inhibit early postoperative recovery by causing hypotension and reducing mobilization. The aim of this study is to determine whether multimodal analgesia with LAC was effective with respect to adequate pain management, and compare its impact on hypotension and mobility. Patients receiving multimodal LAC analgesia were matched using propensity score matching to patients undergoing two-phase trans-thoracic esophagectomy with a TE over a two-year period (from January 2015 to December 2016). Postoperative endpoints that had been evaluated prospectively, including pain scores on movement and at rest, inotrope or vasoconstrictor requirements, and hypotension (systolic BP < 90 mmHg), were compared between cohorts. Out of 14 patients (13 male) that received LAC were matched to a cohort of 14 patients on age, sex, and comorbidity. Mean and maximum pain scores at rest and movement on postoperative days 0 to 3 were equivalent between the groups. In both cohorts, 50% of patients had a pain score of more than 7 on at least one occasion. Fewer patients in the LAC group required vasoconstrictor infusion (LAC: 36% vs. TE: 57%, P = 0.256) to maintain blood pressure or had episodes of hypotension (LAC: 43% vs. TE: 79%, P = 0.05). The LAC group was more able to ambulate on the first postoperative day (LAC: 64% vs. TE: 43%, P = 0.14) but these differences were not statistically significant. Within the epidural cohort, three patients had interruption of epidural due to dislodgement or failure of block compared to no disruption in the multimodal local anesthesia catheters group (P = 0.05). Therefore, multimodal anesthesia using spinal diamorphine with combined paravertebral and rectus sheath local anesthetic catheters appears to provide comparable pain relief post two-phase esophagectomy and may provide more reliable and safe analgesia than the current standard of care.

Impact of supplemental home enteral feeding postesophagectomy on nutrition, body composition, quality of life, and patient satisfaction.

The aim of this prospective cohort study is to analyze the impact of supplemental home enteral nutrition (HEN) post-esophageal cancer surgery on nutritional parameters, quality of life (QL), and patient satisfaction. A systematic review reported that over 60% of patients lose >10% of both body weight and BMI by 6 months after esophagectomy. Enteral feeding (EF) is increasingly a modern standard postoperatively; however, the impact of extended HEN postdischarge has not been systematically studied. One hundred forty-nine consecutive patients [mean age 62 ± 9, 80% male,76% adenocarcinoma, 66% on multimodal protocols, and 69% with BMI ≥ 25 kg/m2] were studied. Jejunal EF commenced day 1 postoperatively, and supplemental overnight HEN (764 kcal; 32g protein) continued on discharge for a planned further 4 weeks. Weight, BMI, and body composition analysis (bioimpedance analysis) were measured at baseline, preoperatively and at 1, 3, and 6 months, along with the EORTC QLQ-C30/OES18 QL measures. A patient satisfaction questionnaire addressed eight key items in relation to HEN (max score 100/item). Median (range) total duration of EF was 49 days (28-96). Overall compliance was 96%. At 6 months, compared with preoperatively, 58 (39%) patients lost >10% weight, with median (IQR) loss of 6.8 (4-9) kg, and 62 (41%) patients lost >10% BMI. Lean body mass and body fat were significantly (p < 0.001) decreased. Mean global QL decreased (p < 0.01) from 82 to 72. A high mean satisfaction score (>70 ± 11/100) was reported, >80 for practical training, activities of daily living, pain, anxiety, recovery and impact on caregivers, with lower scores for appetite (33 ± 24) and sleep (63 ± 30). Supplemental HEN for a minimum of one month postdischarge is associated with high compliance and patient satisfaction. Weight and BMI loss may still be substantial, however this may be less than published literature, in addition the impact on HR-QL may be attenuated. HEN has both subjective and objective rationale and merits further validation toward optimizing nutritional recovery and overall wellbeing.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively. In a subset of 30 patients, circulating levels of IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TGF-ß, and cortisol were measured. Incidences of postoperative complications were prospectively recorded. In the study cohort, 51% of patients were viscerally obese, 40.7% had MetSyn, and 33.6% were hyperglycemic. Viscerally obese and MetSyn-positive patients demonstrated greater postoperative CRP levels and CRP:albumin levels on day 7 and day 14 compared with nonobese and MetSyn-negative patients (P < 0.05). Higher postoperative circulating levels of cortisol were observed in the viscerally obese and hyperglycemic patients compared to nonobese and normoglycemic patients. No association was observed between visceral obesity, MetSyn or hyperglycemia, and postoperative cytokine profile. Viscerally obese patients had an increased overall incidence of postoperative complications compared to nonobese patients (67.2% vs. 47.5%, P = 0.031) on univariate but not multivariate analysis (P = 0.078) and visceral obesity was not associated with an increased incidence of specific complications. Visceral obesity, MetSyn, and hyperglycemia are prevalent in patients undergoing major upper gastrointestinal resection and are associated with an exaggerated acute-phase inflammatory response postoperatively. Further research is warranted to determine whether this association is directly causal.

Lack of independent significance of a close (<1 mm) circumferential resection margin involvement in esophageal and junctional cancer.

BACKGROUND: For rectal cancer, an involved circumferential resection margin (CRM), defined as tumor cells within 1 mm of the CRM, is of established prognostic significance. This definition for the esophagus, however, is controversial, with the UK Royal College of Pathologists (RCP) recommending the 1 mm definition, while the College of American Pathologists (CAP) advises that only tumor cells at the cut margin (0 mm) define an incomplete (R1) resection. The aim of this study was to compare the clinical significance of both definitions in patients with pT3 tumors. METHODS: CAP- and RCP-defined CRM status in patients treated by surgery only or by multimodal therapy was recorded prospectively in a comprehensive database from May 2003 to May 2011. Kaplan-Meier survival curves were generated, and factors affecting survival were assessed by univariate and multivariate analysis. RESULTS: A total of 157 of 340 patients had pT3 esophageal tumors, with RCP-positive CRM in 60 %, and 18 % by CAP. There were no significant differences between RCP-positive CRM and negative margins for node-positive disease, local recurrence, and survival. CAP-positive CRM was associated with positive nodes (P = 0.036) and poorer survival (P = 0.023). Multivariate analysis revealed nodal invasion to be the only independent prognostic variable (P = 0.004). CONCLUSIONS: A CRM margin of <1 mm is common in pT3 esophageal tumors, a finding consistent with other reports. The <1 mm definition was not associated with node positivity, local recurrence, or survival, in contrast to actual involvement at the margin, suggesting lack of independent prognostic significance of the RCP definition and possible superiority of the CAP criteria for prospective registration of CRM.

Acute intestinal failure in surgical patients: an audit of incidence, management and outcomes in an irish hospital, and compliance with ASGBI guidelines.

BACKGROUND: Acute intestinal failure (AIF) is defined as an inability to tolerate 80% of nutritional requirements delivered enterally for a minimum of 48 h. In surgical patients it commonly relates to abdominal sepsis, intestinal obstruction, or ileus. The prevalence of AIF in surgical units in Ireland has not previously been studied. METHODS: We retrospectively audited the general surgical and ICU departments in St James's Hospital over a 3-month period to identify patients with AIF and followed their management and outcomes focusing on the need for artificial nutrition and surgical intervention. RESULTS: Fifty-four surgical patients (11.4% of surgical emergency admissions) were diagnosed with AIF over the 3-month period. Of these, 30 (55.6%) required nutritional support; 26 (48.2%) had surgical ± radiological intervention and 6 (11.1%) had radiological intervention alone. Abdominal sepsis was present in 17 (31.5%) patients, a group that required significantly longer parenteral (14.6 vs. 6.7 days, p 0.029) and enteral (13.9 vs. 2.2 days, p 0.005) nutrition than AIF patients without abdominal sepsis. AIF also took longer to resolve in (5.8 vs. 4.2 days, p 0.024) in sepsis versus nonsepsis patients. The majority of patients (n = 43, 80%) were referred to clinical nutrition teams early after having symptoms for 3.77 days (range 1-21) and 72% had complete nutritional assessment clearly documented. CONCLUSION: AIF is common, and can often be treated conservatively. Early linkage with nutrition services is recommended. Early diagnosis of abdominal sepsis is important as this cohort of patients can be particularly difficult to manage.

Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma.

BACKGROUND: Epidemiological studies have linked obesity with many cancers. The insulin-like growth factor (IGF) 1 axis may be an important mediator in obesity-associated cancer. This study examined the relationship between IGF-1 and its receptor (IGF-1R) in oesophageal adenocarcinoma, a cancer strongly linked to obesity. METHODS: Patients with oesophageal adenocarcinoma considered suitable for attempted curative treatment were studied. Visceral adiposity was defined by waist circumference or visceral fat area. Free and total IGF-1 in serum were measured by enzyme-linked immunosorbent assay. Quantitative polymerase chain resection was used to determine mRNA expression of IGF-1 and IGF-1R in resected tumour samples. IGF-1R expression in tissue microarrays (TMAs) was quantified by immunohistochemistry. RESULTS: A total of 220 patients were studied. Total and free IGF-1 levels were significantly increased in the serum of viscerally obese patients. Gene expression analysis revealed a significant association between obesity status and both IGF-1R (P = 0·021) and IGF-1 (P = 0·031) in tumours. TMA analysis demonstrated that IGF-1R expression in resected tumours was significantly higher in viscerally obese patients than in those of normal weight (P = 0·023). Disease-specific survival was longer in patients with negative IGF-1R expression than in those with IGF-1R-positive tumours (median 60·0 versus 23·4 months; P = 0·027). CONCLUSION: This study highlighted the association of the IGF axis with visceral obesity, and a potential impact on the biology of oesophageal adenocarcinoma through its receptor. Targeting the IGF axis may have a rationale in future studies.

Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue.

Obesity has been associated with increased incidence and mortality of oesophageal and colorectal adenocarcinoma. Excess central adiposity may drive this association through an altered inflammatory milieu. Utilising a unique adipose tissue bioresource we aimed to determine the pro-tumour properties of visceral adipose tissue. Comparing subcutaneous and visceral adipose tissue depots, we observed significantly higher levels of VEGF and IL-6, along with significantly higher proportions of CD8(+) T cells and NKT cells in visceral adipose tissue. Significantly higher levels of VEGF were observed in the conditioned media from visceral adipose tissue of centrally obese compared to non-obese patients. We also report a significant increase in oesophageal and colorectal tumour cell proliferation following culture with conditioned media from visceral adipose tissue of centrally obese patients. Neutralising VEGF in the conditioned media significantly decreased tumour cell proliferation. This novel report highlights a potential mechanism whereby visceral adipose tissue from centrally obese cancer patients may drive tumour progression.

T lymphocyte activation in visceral adipose tissue of patients with oesophageal adenocarcinoma.

BACKGROUND: Visceral adipose tissue may fuel obesity-associated chronic inflammation and tumorigenesis. T cells may be important in visceral adipose tissue in driving inflammation, but they have not yet been characterized in patients with cancer. This study aimed to characterize T lymphocytes in visceral adipose tissue and peripheral blood from patients with oesophageal adenocarcinoma. METHODS: Omental fat was taken from 35 patients with oesophageal adenocarcinoma at the start of surgery. Flow cytometry was performed to assess T cell activation status and cytokine production in omentum and peripheral blood. RESULTS: A large population of lymphocytes was present in the omentum. Omental CD4(+) and CD8(+) T cells displayed significantly enhanced expression of the T cell activation markers CD69 (P < 0·001) and CD107a (CD8(+) T cells: P < 0·01), and significantly decreased CD62L expression (P < 0·05), compared with blood. Significantly higher proportions of CD45RO(+) T cells compared with CD45RA(+) T cells were present in omentum (P < 0·001 and P = 0·012 for CD4(+) and CD8(+) cells respectively). Interferon γ was the most abundant cytokine expressed by omental T cells, with a significantly higher level than in blood and subcutaneous adipose tissue (P < 0·01). CONCLUSION: Visceral adipose tissue is a rich source of activated proinflammatory CD4(+) and CD8(+) T cells. It may fuel chronic inflammation via T cell-mediated pathways.

The impact of young age on outcomes in esophageal and junctional cancer.

It is not known whether patients diagnosed with esophageal and junctional cancer aged younger than 50 years have a more aggressive disease phenotype and thus poorer outcomes following treatment. Prospectively maintained database records of all patients diagnosed with esophageal carcinoma (n= 2129) over a 20-year period (1990-2009) in a single institution were analyzed. Patients aged less than 50 years at diagnosis (n= 170) were compared with those over 50 years with respect to clinicopathological stage and oncological outcomes. There was a significantly greater proportion of male patients (77.4 vs. 64.7%) among the younger group (P= 0.001). Patients were more likely to be diagnosed with an esophagogastric junction tumor (P= 0.002) and to have symptoms for a longer period prior to diagnosis (24.0 vs. 17.8 weeks, P= 0.03) if they were aged less than 50 years old. There was no significant difference in clinicopathological staging including Tumor-Nodal-Metastasis (TNM) stage, differentiation, and lymphatic and perineural invasion other than a greater likelihood of venous invasion in the older group (P= 0.002). Younger patients were more likely to be treated with curative rather than palliative intent (66.9 vs. 51.1%, P < 0.001). The disease-specific survival of patients younger than 50 years treated with curative intent was significantly greater than older patients (median 35 vs. 21 months, P= 0.04), except for the subgroup of patients aged less than 35 years (n= 18) who have reduced survival. Multivariate analysis revealed independent factors related to the difference in survival included sex, age, advanced T stage, and nodal metastases (P < 0.05). A consistent proportion of esophageal cancer patients are diagnosed aged less than 50 years old over time (1990-2009). Few phenotypic tumor differences were noted between the groups. With an aggressive approach to management, survival is significantly greater than in the older cohort, although outcomes are poorer in those aged below 35 years.

Aspirin for lower limb arthroplasty thromboprophylaxis: review of international guidelines.

INTRODUCTION: Aspirin is one of the pharmacological agents used for thromboprophylaxis. MATERIALS AND METHODS: National thromboprophylaxis guidelines, peer-reviewed studies and data from national joint register of England and Wales were analysed for evidence regarding the efficacy of aspirin versus other agents in thromboprophylaxis and the recommendations of guidelines. RESULTS: Two of five guidelines reviewed recommend the use of aspirin for thromboprophylaxis. Aspirin is used as thromboprophylactic agent in approximately 25% of patients undergoing total hip and total knee arthroplasty in year 2006 in England and Wales. There is no difference in mortality in these patients compared to patients on other pharmacological agents. CONCLUSION: There is conflicting evidence and differences in interpretation of the data from the literature. If specific outcome measures and complications such as symptomatic DVT, PE and bleeding were logged in arthroplasty registers, the resulting data would be useful in individualised decision-making.

Diet, obesity and cancer.

INTRODUCTION AND AIMS: Obesity and the rising incidence of certain cancers are the manifest expressions of problems with diet and lifestyle. A number of complex and closely inter-related factors mediate the association between environment and cancer development. This review seeks to summarise the current evidence pertaining to dietary factors and cancer incidence and progression. METHODS: Relevant literature was identified by search of the Pubmed database using the terms: diet, cancer, carcinogenesis, tumourigenesis. References from relevant articles were searched. Selection of articles was based on peer review, journal and relevance. Where possible, meta-analyses of randomised controlled trials (RCTs) or large RCTs were cited preferentially. RESULTS: Variations in cancer trends between geographic regions and in migration studies point to the key role of environmental differences in cancer incidence. Mechanisms of tumorigenesis, including inflammation, angiogenesis, may be influenced by specific dietary constituents including glucosinolates, organosulphur compounds, genistein, curcumin, catechins, resveratrol and lycopene. CONCLUSION: Despite epidemiological evidence suggesting a link between dietary factors and cancer development, confounding factors such as obesity, physical activity and the sheer variety of bioactive compounds in a normal diet pose a great challenge to the study of mechanisms linking diet and cancer. A greater understanding of the interplay between dietary constituents and cancer development should un-cover new targets for the prevention and treatment of cancer.

Palliative endoscopic trans-anal resection of advanced rectosigmoid carcinoma.

There is no consensus on optimal treatment of patients with rectosigmoid cancer and unresectable metastatic disease. This is a retrospective review of all patients who underwent palliative endoscopic trans-anal resection (ETAR) of rectosigmoid cancer over a 10-year period. Fourteen patients (11 male) with a mean age 69.7 years (range 51-86) underwent ETAR; 11 for rectal tumours and 3 for rectosigmoid tumours. Indications included tenesmus (5), troublesome bleeding (6), mucous discharge (1) and obstructed defaecation (8). The number of treatment episodes varied from 1 to 4 (median 1). The symptom-free interval was mean 6.25 months (range 2-15). Eight patients had lifelong relief of symptoms and four patients are currently symptom free. There were two short-term failures treated with stenting (1) and abdominoperineal resection (1). There were no immediate post-treatment complications. One patient developed increasing incontinence and another pelvic pain after ETAR attributable to local tumour infiltration. ETAR provides a convenient and safe method of palliation for patients with local symptoms of advanced rectosigmoid carcinoma.

Eversion endarterectomy for external iliac artery occlusive disease.

INTRODUCTION: The advent of effective endovascular techniques has revolutionized the treatment of iliac occlusive disease. Long-segment iliac occlusions remain technically difficult to treat, particularly in the presence of femoral disease. Iliac endarterectomy is an established procedure for the treatment of iliac occlusive disease, but it has been suggested that in the era of effective endovascular intervention, its role is limited. METHODS: A review of all patients who had eversion endarterectomy of the external iliac artery from a single institution between 2000 and 2008. RESULTS: Twenty-one patients (18 male) underwent eversion external iliac endarterectomy, 15 for external iliac and 6 for iliofemoral disease. Mean age was 64.7 years (range: 46-78 years) and the modal American Society of Anaesthesiologists (ASA) grade was 3. The indications were critical ischemia (n = 16) and disabling claudication (n = 5). Twelve had adjunctive procedures. The mean follow-up was 25.3 months (range: 1-59 months). There were no technical failures. Seventeen patients had significant improvement in symptoms and three had moderate improvement. The cumulative primary patency at 1 year was 81%. One patient had no improvement (because of infrainguinal occlusive disease), and subsequently required femoro-popliteal bypass. There was no systemic morbidity within 30 days. There was 1 in-hospital death from sudden cardiac arrest (47 days postoperatively). Six patients died during follow-up (from unrelated illness). CONCLUSION: Eversion external iliac endarterectomy is an effective means of treating iliofemoral occlusive disease with excellent short-term outcomes and a low complication rate in a cohort with high levels of comorbidity.

European Working Time Directive: implications for surgical training.

The forthcoming implementation of the European Working Time Directive (EWTD) for non-consultant hospital doctors (NCHDs) poses a number of challenges in the areas of patient care, training, service provision and quality of life for workers. Surgery, as a craft-based speciality, will face a greater impact on training of future surgeons as operating time could be lost to service provision. The EWTD acts a stimulus for reform of current working practices and re-configuration of services. It will necessitate transformation of the way in which surgeons are trained, if current standards are to be maintained.

Obesity and gastrointestinal cancer.

BACKGROUND: There is emerging evidence of a strong association between obesity and gastrointestinal cancer. This review summarizes the evidence from an epidemiological and pathophysiological perspective. METHODS: Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles were identified. Selection of articles was based on peer review, journal and relevance. RESULTS: Numerous epidemiological studies consistently identified an increased risk of developing oesophageal adenocarcinoma and colorectal carcinoma in the obese. The association between obesity and other gastrointestinal malignancies was less robust. Sex seems important with respect to cancer risk. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the insulin-like growth factor axis, adipocytokines and sex steroids. CONCLUSION: A better understanding of the mechanisms that link obesity and cancer may uncover targets for intervention. Tackling obesity may result in a reduction in the incidence in addition to mortality of certain cancers in future.